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12. Fructose-functionalized polymers to enhance therapeutic potential of p-boronophenylalanine for neutron capture therapy

Author

Nomoto, Takahiro, YAO, Ying, Yao, Ying, Inoue, Yukiya, Suzuki, Minoru, Kanamori, Kaito, Takemoto, Hiroyasu, Matsui, Makoto, Tomoda, Keishiro, and Nishiyama, Nobuhiro

Subjects
Boron Compounds, Polymers, Phenylalanine, Pharmaceutical Science, Boron Neutron Capture Therapy, 02 engineering and technology, Fructose, Endocytosis, 03 medical and health sciences, chemistry.chemical_compound, Mice, Animals, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Cationic polymerization, Polymer, 021001 nanoscience & nanotechnology, Amino acid, Neutron capture, chemistry, Drug delivery, Biophysics, 0210 nano-technology, Ethylene glycol
Abstract

In boron neutron capture therapy (BNCT), boron drugs should accumulate selectively within a tumor and be quickly cleared from blood and normal organs. However, it is usually challenging to achieve the efficient tumor accumulation and the quick clearance simultaneously. Here we report the complex composed of a fructose-modified poly(ethylene glycol)-poly(l-lysine) block copolymer and p-boronophenylalanine, termed PEG-P[Lys/Lys(fructose)]-BPA, as a boron delivery system permitting selective accumulation within the target tumor with quick clearance from normal organs as well as blood. Our PEG-P[Lys/Lys(fructose)]-BPA could be internalized into tumor cells through LAT1 amino acid transporter-mediated endocytosis and retain in the targeted cells, thereby accomplishing more efficient accumulation and retention in a subcutaneous tumor than clinically used fructose-BPA complexes. Importantly, the moderately cationic property of the polymer facilitated renal clearance and PEG-P[Lys/Lys(fructose)]-BPA exhibited high accumulation contrast between the target tumor and the blood/normal organ. Finally, upon thermal neutron irradiation, PEG-P[Lys/Lys(fructose)]-BPA significantly inhibited the tumor growth in mice. PEG-P[Lys/Lys(fructose)]-BPA may be a promising boron delivery system for BNCT.

Published
2021

24. Selective delivery of rifampicin incorporated into poly(dl-lactic-co-glycolic) acid microspheres after phagocytotic uptake by alveolar macrophages, and the killing effect against intracellular Mycobacterium bovis Calmette–Guérin

Author

Yoshida, Aya, primary, Matumoto, Makoto, additional, Hshizume, Hiroyuki, additional, Oba, Yoshiro, additional, Tomishige, Tatuo, additional, Inagawa, Hiroyuki, additional, Kohchi, Chie, additional, Hino, Mami, additional, Ito, Fuminori, additional, Tomoda, Keishiro, additional, Nakajima, Takehisa, additional, Makino, Kimiko, additional, Terada, Hiroshi, additional, Hori, Hitoshi, additional, and Soma, Gen-Ichiro, additional

Published
2006
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